The objectives of this research are (1) to determine whether human fibroblasts from normal and diabetic subjects exhibit intrinsic variations in the structure and quality of secreted collagen, and (2) to examine the effect of potential nutritional and hormonal modulators on collagen metabolism in these cells. In preliminary studies, we have examined collagen metabolism in human fibroblasts during their attachment to a solid substrate by quantitation of the total hydroxylation of proline and lysine. We propose to compare the collagen proteins secreted by normal and diabetic fibroblasts cultured in vitro, with respect to the type and quantity synthesized by each cell type. We will also investigate various hormonal and nutritional effectors as potential modulators of collagen metabolism in normal and diabetic cells. It is considered that these studies may help to elucidate and underlying biochemical mechanisms by which collagen metabolism is regulated as well as to provide information relevant to the abberration of this metabolism which occurs as a characteristic lesion associated with diabetic microangiopathy.